Itch (pruritus) is perhaps the most common symptom associated with a majority of these inflammatory skin diseases, and acute as well as chronic stress perceptions are recognized to trigger or enhance pruritus.

A wealth of mediators released systemically or locally in the skin in response to stress increase sensory innervation, upregulate the production of other pruritogenic agents, perpetuate (neurogenic) inflammation and lower the itch threshold.

In the present review, we explore recent frontiers in both stress and pruritus research and portray the perpetuation of chronic skin inflammation and itch as a neuroendocrine-immune ‘misalliance’.

We argue that key candidate molecules of the stress response with strong pruritogenic potential, such as nerve growth factor, corticotropin-releasing hormone and substance P, and mast cells, which may be considered as ‘central cellular switchboards of pruritogenic inflammation’, need to be further explored systematically in order to develop more effective therapeutic combination strategies for itch management in chronic, stress-vulnerable inflammatory skin diseases.

Interest in the hair follicle (HF) has recently increased, yet the detailed mechanisms of HF function and immune privilege (IP) have not yet been elucidated.

This review discusses the critical points of immunobiology and hormonal aspects of HFs. The HF is a unique mini-organ because it has its own immune system and hormonal milieu.

In addition, the HF immune and hormonal systems may greatly affect skin immunobiology. Therefore, knowledge of HF immunobiology and hormonal aspects will lead to a better understanding of skin biology.

The HF has a unique hair cycle (anagen, catagen and telogen) and contains stem cells in the bulge area. The HF is closely related to sebaceous glands and the nervous system.

This article reviews the interaction between the endocrine/immune system and HFs, including the pathogenesis of alopecia areata associated with stress.

Whether this is of any relevance in human hair follicles (HFs) is completely unclear. Therefore, we have investigated the effects of substance P, the central cutaneous prototypic stress-associated neuropeptide, on normal, growing human scalp HFs in organ culture.

We show that these prominently expressed substance P receptor (NK1) at the gene and protein level.

Pruritus is a common symptom reported in connective tissue and other common systemic disease states. Unfortunately, the unique pathophysiologic etiology of the often chronic and severe pruritus that is a debilitating component of many connective tissue disorders makes treatment with conventional anti-itch agents difficult. As the underlying mechanisms of pruritus have been identified, treatment strategies have evolved. Considering the diversity of available antipruritic therapies and the variability of underlying factors specific to disease states, individualized therapy recommendations are necessary. Important new areas of treatment target the central and peripheral mechanisms of pruritus and include anticonvulsants, antidepressants, opioid antagonists, and phototherapy Further research is necessary to quantify the role of new and novel antipruritic therapies.

In humans, as in all mammals and most chordates, three forms of superoxide dismutase (SOD) are present: SOD1 is located in the cytoplasm, SOD2 in the mitochondria, and SOD3 is extracellular. SOD is used in cosmetic products to reduce free radical damage to the skin, for example, to reduce fibrosis following radiation for breast cancer. Pruritus is one of the most common symptoms of skin diseases, but can also be a major symptom of systemic diseases (e.g., malignancy, infection or metabolic disorders). There are various antihistaminics used as antipruritogenic substances. In the genesis of pruritus there are many pruritogens involved, not only histamine and leukotrienes such as acetylcholine, cytokines, kallikreins, proteases, kinins, opioids, etc., which are described. On many occasions, we observed that topical SOD seemed to possess strong antipruritic activity, even in anti-histamine-resistant pruritus. We analyzed literature data on the effect of SOD as an anti-pruritogen on NK-1 receptors and proinflammatory cytokines, its regulatory role in calcitonin gene-related peptide production and expression, down-regulation of TNF- and numerous cytokines, and suppression of nitric oxide production.

The HECT-type E3 ubiquitin ligase (E3) Itch is absent in the non-agouti-lethal 18H or Itchy mice, which develop a severe immunological disease, including lung and stomach inflammation and hyperplasia of lymphoid and hematopoietic cells. The involvement of Itch in multiple signaling pathways and pathological conditions is presently an area of extensive scientific interest. This review aims to bring together a growing body of work exploring Itch-regulated biological processes, and to highlight recent discoveries on the regulatory mechanisms modulating its catalytic activity and substrate recognition capability. Our contribution is also an endeavor to correlate Itch substrate specificity with the pathological defects manifested by the mutant Itchy mice.